Brain and Central Nervous System TumorsPhase 1NCT00458744
Talotrexin in Treating Young Patients With Recurrent Solid Tumors or Leukemia That is Recurrent or Does Not Respond to Treatment
A Phase 1 study testing talotrexin and chemotherapy in people with Brain and Central Nervous System Tumors and Leukemia, run by Children's Oncology Group.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as talotrexin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors, Leukemia, Lymphoma
- What is being tested?
- talotrexin and chemotherapy
- Type of treatment
- Surgery or procedure
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Feb 2007to Jul 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Diagnosis of either of the following:
- Recurrent solid tumor
- Histologically confirmed* malignancy at original diagnosis or relapse
- Measurable or evaluable disease
- Lymphoma or primary CNS tumor allowed
- Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for the past 7 days
- Recurrent or refractory leukemia
- Confirmed relapse, as defined by M3 marrow (25% blasts in bone marrow aspirate or biopsy)
- Active extramedullary disease allowed provided there is no leptomeningeal involvement NOTE: *Histological confirmation not required for intrinsic brain stem tumors
- Bone marrow metastases allowed
- Not refractory to red blood cell or platelet transfusion
- No pleural effusion or significant ascites
- No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
- No Down syndrome
PATIENT CHARACTERISTICS:
- Karnofsky performance status (PS) 50-100% (for patients > 10 years of age) OR Lansky PS 50-100% (for patients ≤ 10 years of age)
- Absolute neutrophil count ≥ 1,000/mm³ (for patients with solid tumors without bone marrow involvement)
- Platelet count ≥ 100,000/mm³ (transfusion independent)
- Hemoglobin ≥ 8.0 g/dL
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine adjusted according to age as follows:
- No greater than 0.6 mg/dL (1 year to 23 months)
- No greater than 0.8 mg/dL (2 to 5 years)
- No greater than 1.0 mg/dL (6 to 9 years)
- No greater than 1.2 mg/dL (10 to 12 years)
- No greater than 1.4 mg/dL (13 years and over [female])
- No greater than 1.5 mg/dL (13 to 15 years [male])
- No greater than 1.7 mg/dL (16 years and over [male])
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT ≤ 110 U/L (ULN is 45 U/L)
- Albumin ≥ 2 g/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled infection
- No known condition that, in the opinion of the investigator, would preclude study compliance
PRIOR CONCURRENT THERAPY:
- Recovered from all prior treatment-related toxicity
- At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea) (for patients with solid tumors)
- At least 24 hours since prior cytoreduction therapy initiated with hydroxyurea (for patients with leukemia)
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 6 months since prior total-body irradiation (TBI), craniospinal radiotherapy, or ≥ 50% radiotherapy to the pelvis
- At least 6 weeks since prior substantial bone marrow radiotherapy
- At least 3 months since prior stem cell transplant or rescue without TBI
- No evidence of active graft-versus-host disease
- At least 7 days since prior growth factor therapy
- At least 7 days since prior biological therapy
- No nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin or other salicylates, penicillins, sulfa drugs (bactrim, septra), ciprofloxacin, tetracycline, thiazide diuretics, or probenecid within 2 days prior to, during, or within 5 days after treatment with talotrexin
- No long-acting NSAIDs (e.g., nabumetone, naproxen, oxaprozin, piroxicam) within 5 days prior to, during, or within 5 days after treatment with talotrexin
- No concurrent investigational drugs
- No concurrent anticancer agents or therapy (e.g., chemotherapy, radiotherapy, immunotherapy, or biologic therapy)
About this study
Official title: A Phase I Study Of Talotrexin (PT-523) In Children And Adolescents With Recurrent Solid Tumors Or Recurrent/Refractory Leukemias
RATIONALE: Drugs used in chemotherapy, such as talotrexin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of talotrexin in treating young patients with recurrent solid tumors or leukemia that is recurrent or does not respond to treatment.
Read the detailed description
OBJECTIVES:
Primary
- Estimate the maximum tolerated dose (MTD) and recommended phase II dose of talotrexin in younger patients with recurrent solid tumors or recurrent or refractory leukemia.
- Determine the toxicity of this drug in these patients.
Secondary
- Determine the antitumor activity of this drug in these patients.
- Assess the tolerability of the defined MTD of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to diagnosis (solid tumor vs leukemia).
- Stratum 1 (recurrent solid tumor): Patients receive talotrexin IV over 10 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of talotrexin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).
- Stratum 2 (recurrent or refractory leukemia): A cohort of 3-6 patients with leukemia receive treatment as in stratum 1 at the MTD determined in stratum 1. If 2 or 3 or 2 of 6 patients experience a DLT at the solid tumor MTD, accrual is stopped.
After completion of study treatment, patients are followed for 30 days.
PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.
- Conditions
- Brain and Central Nervous System Tumors, Leukemia, Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific
- Being tested
- talotrexin, chemotherapy
- Keywords
- juvenile myelomonocytic leukemia, relapsing chronic myelogenous leukemia, unspecified childhood solid tumor, protocol specific, childhood chronic myelogenous leukemia, childhood acute promyelocytic leukemia (M3), recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, childhood central nervous system germ cell tumor, childhood choroid plexus tumor, childhood craniopharyngioma, childhood infratentorial ependymoma, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma, childhood supratentorial ependymoma, recurrent childhood brain stem glioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood ependymoma, recurrent childhood medulloblastoma
- Medical subject headings
- Central Nervous System Neoplasms, Leukemia, Lymphoma, Leukemia, Myelomonocytic, Juvenile, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Choroid Plexus Neoplasms, Astrocytoma, Familial ependymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
talotrexinDrug
chemotherapyProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of talotrexin
Toxicity
Secondary outcomes (2)
Antitumor activity
Tolerability
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2007 (estimated)
- Study startFeb 2007
- Primary completionJul 2008 (estimated)
Why it stopped: Study withdrawn because of toxicity reported on the adult phase 1 trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- James Croop, MD, PhD, Study chair, Riley's Children Cancer Center at Riley Hospital for ChildrenSultan Ahmed Pradhan, MD, Study chair, Tata Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00458744
- Sponsor's protocol ID
- ADVL0613
- Other IDs
- COG-ADVL0613, CDR0000538359
- Status last verified
- Aug 2014
- First submitted
- 9 Apr 2007
- Last updated
- 8 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Of Talotrexin (PT-523) In Children And Adolescents With Recurrent Solid Tumors Or Recurrent/Refractory Leukemias
- ClinicalTrials.gov ID
- NCT00458744
- Acronym / sponsor ID
- ADVL0613
- Conditions
- Brain and Central Nervous System Tumors, Leukemia, Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific
- Keywords
- juvenile myelomonocytic leukemia, relapsing chronic myelogenous leukemia, unspecified childhood solid tumor, protocol specific, childhood chronic myelogenous leukemia, childhood acute promyelocytic leukemia (M3), recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, childhood central nervous system germ cell tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn because of toxicity reported on the adult phase 1 trial.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2007
- Primary completion
- Jul 2008 (estimated)
- First posted
- 11 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as talotrexin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of talotrexin in treating young patients with recurrent solid tumors or leukemia that is recurrent or does not respond to treatment.
Detailed description
OBJECTIVES:
Primary
- Estimate the maximum tolerated dose (MTD) and recommended phase II dose of talotrexin in younger patients with recurrent solid tumors or recurrent or refractory leukemia.
- Determine the toxicity of this drug in these patients.
Secondary
- Determine the antitumor activity of this drug in these patients.
- Assess the tolerability of the defined MTD of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to diagnosis (solid tumor vs leukemia).
- Stratum 1 (recurrent solid tumor): Patients receive talotrexin IV over 10 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of talotrexin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).
- Stratum 2 (recurrent or refractory leukemia): A cohort of 3-6 patients with leukemia receive treatment as in stratum 1 at the MTD determined in stratum 1. If 2 or 3 or 2 of 6 patients experience a DLT at the solid tumor MTD, accrual is stopped.
After completion of study treatment, patients are followed for 30 days.
PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| talotrexin | Drug | – |
| chemotherapy | Procedure or surgery | – |
Primary outcome
Maximum tolerated dose of talotrexin
Toxicity
2 secondary outcomes
Antitumor activity
Tolerability
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Croop, MD, PhD study chair
Riley's Children Cancer Center at Riley Hospital for Children
Sultan Ahmed Pradhan, MD study chair
Tata Memorial Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing talotrexin and chemotherapy in people with Brain and Central Nervous System Tumors and Leukemia, run by Children's Oncology Group.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 8 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose of talotrexin. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2014.